Establishment and characterization of a new human megakaryoblastic cell line (SET-2) that spontaneously matures to megakaryocytes and produces platelet-like particles

Abstract

A new factor-independent megakaryoblastic cell line, designated SET-2, was established from the peripheral blood of a patient with leukemic transformation of essential thrombocythemia (ET). SET-2 expressed CD 4, 7, 13, 33, 34, 36, 38, 41, 61, 71, 117, 126, 130 and c-mpl. In addition, it spontaneously produced numerous platelet-like particles in liquid culture. These particles were shown to be the same size as normal platelets, and to express CD 36, 38, 41, 61 and 71. Proliferation of SET-2 was not influenced by thrombopoietin (TPO) and other hemopoietic cytokines. SET-2 was found to express the platelet-specific proteins such as platelet factor 4 and ␤-thromboglobulin. The levels of expression were not altered by TPO. SET-2 also secreted interleukin-6 into the supernatants, as well as normal megakaryocytes. These results suggest that SET-2 spontaneously matures to megakaryocytes and produces platelet-like particles. These findings indicate that SET-2 may be useful for investigating the proliferation and differentiation mechanisms of leukemia cells and the role of c-mpl on megakaryoblasts, megakaryocytes, and platelets in ET. Leukemia (2000) 14, 142-152.

AKT is a therapeutic target in myeloproliferative neoplasms

“…HEL and SET2 cells (37) were grown in RPMI-1640 with 10% fetal bovine serum (FBS). 293T cells were grown in DMEM with 10% FBS.…”

TG02, a novel oral multi-kinase inhibitor of CDKs, JAK2 and FLT3 with potent anti-leukemic properties

“…The effects on JAK-STAT signaling were studied in Karpas 1106P (hyper-activated wild-type JAK2) 16 and SET-2 cells (constitutively phosphorylated JAK2 V617F ) 17 and compared with TG101348. In Karpas 1106P, the IC 50 for pJAK2 (Y1007/8) and pSTAT3 inhibition by TG02 was 63 and 53 nM, respectively, compared with 150 and 90 nM for TG101348 (Figure 4c …”

JAK2 V617F tyrosine kinase mutation in cell lines derived from myeloproliferative disorders

“…Cell lines were tested for JAK2 V617F expression applying the PCR-based ARMS system, a method that specifically amplifies the normal and mutant sequences plus a positive control band in a single reaction. 5 According to ARMS and direct sequencing of genomic PCR products, 5/79 cell lines carried the JAK2 V617F mutation (Figure 1a and b): MB-02 derived from a patient with a history of IM and myeloid metaplasia that developed into AML M7; 14 MUTZ-8 established from a patient with AML M4 25 years after the onset of MDS; 18 SET-2 from a patient at the stage JAK2 V617F mutation in cell lines H Quentmeier et al of leukemic transformation of ET; 19 and UKE-1 from a patient with ET, which transformed into acute leukemia. 20 The AML M6-derived cell line HEL was the only JAK2 V617F positive cell line tested lacking a known patient-history of MPD or MDS.…”